The concentrations of total and respirable airborne endotoxin in the breathing zone of a pony in 3 different management systems, on 8 occasions, are reported. Airborne endotoxin concentrations in all 3 systems were lower than those reported for many other agricultural environments. However, total airborne endotoxin concentrations in many of the conventional stables exceeded those which can induce puImonary inflammation and bronchial hyper-responsiveness in normal human subjects, and exceeded those which can induce bronchoconstriction in humans with pre-existing pulmonary inflammation. Therefore, airborne endotoxin may contribute to the development of airway inflammation and dysfunction in conventionally stabled horses. Potentially detrimental effects of airborne endotoxins on the welfare and exercise performance of stabled horses can be reduced by maintaining horses in 'low dust' stables or at pasture, since these environments had significantly lower airborne dust and endotoxin concentrations.

fibrolamellar carcinoma drug repurposing pediatric rare tumors patient derived xenografts drug screening fusion gene Abbreviations: ATR -Ataxia telangiectasia and Rad3-related protein AURKA -Aurora kinase A AURKB -Aurora kinase B Bcl-xL -B-cell lymphoma-extra large encoded by the BCL2-like 1 gene Bcl2 -B-cell lymphoma 2 ITS -Insulin, (human) Transferrin, Selenium BID -BH3 Interacting Domain Death Agonist BIM -Bcl-2-like protein 11 CA12 -Carbonic anhydrase 12 CDc7 -Cell division cycle 7-related protein kinase CDK -Cyclin depedent protein kinase Cyp19A1 -Also know as aromatase or estrogen synthase DAB -3,3'-Diaminobenzidine DMSO -Dimethyl sulfoxide DNA-PK -DNA protein kinase EGFR -Epidermal growth factor receptor eIF4F -Eukaryotic initiation factor 4F ErbB2 -erythroblastic oncogene B, also known as Her-2 protooncogene Neu and as epidermal growth factor receptor-2 FLC -fibrolamellar hepatocellular carcinoma H&E -hematoxylin and eosin HSA -Highest Single Agent HCC -hepatocellular carcinoma HDAC -Histone deacetylase HSP70 -Heat Shock Protein 70

4111 Background: Fibrolamellar Carcinoma (FLC) is a rare form of primary liver cancer affecting children and young adults that often presents at an advanced stage and even with surgery has an 80% relapse rate. Unresectable FLC patients are considered incurable and have short life expectancy. Effective neoadjuvant and adjuvant systemic therapies are needed to increase chances at remission and protect against relapse. Because of success as single agents in HCC, we tried the combination of nivolumab (NIV) and lenvatanib (LEN) in FLC patients who had exhausted more common therapies. Our objective is to describe our experience using combination NIV-LEN in FLC patients. Methods: Over the last 5 years we have seen over 90 patients with FLC at our institution. After securing IRB approval, (ORA Number: 19071603-IRB01), we collected data in a de-identified fashion for all patients who had received NIV-LEN. Results: Twenty patients (6M/14F), median age at diagnosis/start of NIV-LEN 17/20 (7-52) have received at total of 349 cycles of NIV-LEN (NIVO 3mg/kg IV q2 weeks) and lenvatanib 8mg po daily, 5 adjuvant, 14 neoadjuvant and one both. All had cross sectional imaging every 3 months with independent review. The median number of cycles/months of follow up was 19.5 (3-43)/13.5 (3-31) respectively. The median number of prior relapses, systemic therapies, prior abdominal surgeries, and prior radiation (IR ablations, TARE, TACE, SBRT) were 3.5 (0-7), 3 (0-11), 2 (0-6), and 2.5 (0-13) respectively. Three patients had gemcitabine added to NIVO-LEN for part ( < 1/3) of their regimen. The best response by RECIST 1.1 of the 14 neoadjuvant patients was 3 CR, 3 PR, 7 SD and 2 PD, for an overall response rate (PR + CR) of 40% and overall control rate (CR + PR + SD) of 87%. Seven of 20 (30%) stopped NIVO-LEN [PD (3), infection (2), or patients’ wishes (2)] while 14 (70%) continue, including all adjuvant patients who remain in CR (median follow-up of 10 months). The 6-, 12-, and 24-month progression free survival (PFS) and overall survival (OS) were: (70%,49%,49%) and (94%,94%,73%) respectively. For 14 of 17 (82%) relapsed patients, the PFS was longer than the patients’ most recent PFS, and longest ever in 9 (53%). Six of the 14 initial non-surgical candidates (43%) either had surgery (2), or avoided surgery (3 CR, 1 ablation). There were 2 grade 3 toxicities (both infections) and no grade 4 toxicities. The most common toxicities were hypertension and fatigue in 25% and 20% respectively. One patient, after 5 relapses, had more than 120 lung nodules > 1cm that after 14 months of NIVO-LEN achieved CR and has remained in CR for another 14 months. Conclusions: Our retrospective experience with the novel immune-chemotherapy combination of NIV-LEN for FLC in an extremely rare disease with no proven systemic therapies is encouraging, especially for those who are not surgical candidates or in a surgical remission. We hope this report can inform future prospective trials in treating this deadly disease.

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3034 Background: Fibrolamellar Carcinoma (FLC) is an extremely rare form of primary liver cancer (50-200 cases/year), unrelated to hepatocellular carcinoma. The only established standard of care is surgery. However, recurrence is at least 80%, even with R0 surgery, suggesting that FLC is best thought of as a systemic disease instead of a surgical disease. Systemic therapies in retrospective studies of more than 25 show immunotherapy and chemotherapy combinations have promise. Circulating “tumor-informed” tumor DNA (ctDNA) is a tool for tracking microscopic systemic disease, serving as a marker of systemic involvement, has shown success in management of other cancers. FLC has never been studied using this technology. Our retrospective study of 51 patients over a 2.5-year period is the first attempt to understand if ctDNA can be helpful in the management of FLC. Methods: All patients consented to blood draws on a 1-3 monthly basis, according to the company (Signatera) protocol. All patients had regular imaging reviewed by the FibroFighters Foundation National Tumor Board. Complete response (CR), Partial response (PR) (> 30% decrease), Progressive Disease (PD) (> 20% increase), and Stable Disease (SD) (neither PD/PR/CR) were recorded according RECIST 1.1. The imaging closest in time to the blood draw was used for correlation purposes. “Negative” is defined as a value = 0.00. “Positive” is defined as a value > 0.00. Results: Fifty-one FLC patients (26M, 25F, median age 23, range 10-56), 92% stage (III/IV), consented to ctDNA “blood biopsies,” (n=226 samples, mean 4.4/patient, range 1-11). Negative values correlated with no evidence of disease (NED) on imaging 78% of the time, positive values with disease 94% [PPV/NPV/sens/spec of 0.78/0.94/0.93/0.81]. NPV and sens increased to almost 100% with a ctDNA threshold of > 1.0 at the expense of a lower PPV and spec. However, consecutive negative ctDNA values correlated with radiologic NED 86% [PPV/NPV/sens/spec = 0.86/0.84/0.77/0.91] without a single PD in this cohort (n=64). A “downward trend or slope” on consecutive values predicted Objective Response (CR+PR) and Disease Control (CR+PR+SD) at 68% and 96% [PPV/NPV/sens/spec of 0.68/0.49/0.36/0.78 and 0.96/0.26/0.36/0.94, respectively], while an “upward trend” performed less well to predict relapse [PPV/NPV/sens/spec = 0.54/0.98/0.94/0.81]. Conclusions: In this first exploration of 51 young FLC patients, and 226 tissue-informed cell free ctDNA data points, “Positive” and “Negative” values overall performed well for predicting RECIST 1.1 “disease” or “NED” respectively, especially for consecutive values of zero, where no progressions were observed in 64 distinct FLC scenarios. A downward trend or “slope” performed better than an upward trend to predict objective response (PR+CR) versus relapse (PD).